ESMO14: Phase III rolapitant trial demonstrates significant reductions in nausea and vomiting

The results of a Phase III trial of rolapitant use in cancer patients receiving cisplatin-based chemotherapy were announced recently at the 2014 European Society for Medical Oncology (ESMO) Congress (held 26–30 September, Madrid, Spain).

The randomized multicentre trial was conducted in 532 patients who received rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to cisplatin-based chemotherapy across the US, Asia, South Africa and Europe. Rolapitant, the novel antagonist of the NK-1 receptor, was demonstrated to significantly reduce nausea and vomiting in a significant numbers of cancer patients.

Cisplatin is known to be a strong inducer of emesis (vomiting), and both nausea and emesis are side effects commonly experienced by patients receiving cisplatin-based chemotherapy. In patients who are particularly sensitive to cisplatin, doses may be reduced or treatment may even be terminated.

Improvements were also observed in the quality of life of patients, which was assessed by Functional Living Index-Emesis Questionnaires. Overall, 72.8% of patients receiving rolapitant reported that chemotherapy had less of an impact on their daily quality of life, compared with 67.8% of patients receiving the placebo drug.

Lead author Martin Chasen (medical director, Palliative Care, Ottawa Hospital Cancer Centre, Canada) commented: “One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”

The primary endpoint of the study was defined as patients having no emesis and not requiring any rescue medication (a complete response) in the >24–120 hour delayed phase postchemotherapy. This endpoint was met with 72.7% of patients receiving rolapitant achieving a complete response compared with 58.4% of those receiving the placebo (p < 0.001).

This complete response rate was also met in the acute phase (0–24 hours) in 83.7% of patients receiving rolapitant compared with 73.7% of placebo patients. After 120 hours, 70.1% of rolapitant patients showed a complete response compared with 56.5% placebo patients. In both phases, the results of rolapitant on complete response were demonstrated to be significant (p = 0.005 and 0.001 respectively).

Chasen commented: “Rolapitant demonstrated a significant effect in both the acute and delayed phases. Our primary endpoint was achieved in the delayed phase, an incredible result. We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting – there are other agents that block this for a short time; rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”

Following chemotherapy some patients require the administration of nutrients due to malnourishment and dehydration from severe emesis. Chasen further points out that the use of rolapitant could save costs by enabling patients to eat and drink properly.

These findings suggest that rolapitant could be tested further for use in weaker emesis-inducing chemotherapy methods. In future clinical practice, rolapitant could lead to better prevention of chemotherapy-induced nausea and vomiting, and therefore better toleration of chemotherapy overall. As Chasen emphasizes: “We must treat nausea and vomiting, not just the cancer.”

Sources: Chasen M, Gridelli C, Hedley M et al. Phase 3 (P04832) trial results for rolapitant, novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy. Abstract LBA47, European Society for Medical Oncology Congress (2014); European Soceity for Medical Oncology press release